期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 155, 期 -, 页码 503-515出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2018.06.026
关键词
Dihydropyrimidinones; Organoselenium; Cytotoxicity; DNA damage; Cell cycle arrest; Apoptosis; Selenoureas
资金
- CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior)
- CNPq Grant (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) Brazil
Novel pyrimidinic selenoureas were synthesized and evaluated against tumour and normal cell lines. Among these, the compound named 3j initially showed relevant cytotoxicity and selectivity for tumour cells. Three analogues of 3j were designed and synthesized keeping in view the structural requirements of this compound. Almost all the tested compounds displayed considerable cytotoxicity. However, 8a, one of the 3j analogues, was shown to be highly selective and cytotoxic, especially for breast carcinoma cells (MCF-7) (IC50 = 3.9 mu M). Furthermore, 8a caused DNA damage, inhibited cell proliferation, was able to arrest cell cycle in S phase, and induced cell death by apoptosis in human breast carcinoma cells. Moreover, predictions of pharmacokinetic properties showed that 8a may present good absorption and permeation characteristics for oral administration. Overall, the current study established 8a as a potential drug prototype to be employed as a DNA interactive cytotoxic agent for the treatment of breast cancer. (C) 2018 Elsevier Masson SAS. All rights reserved.
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